Molecular pathways that control platelet production

Upregulation of ribosomal biogenesis (generation of the cellular machinery that makes proteins) is essential for the proliferation and survival of cancer cells. CX-5461 is a first-in-class small molecule inhibitor of RNA Polymerase-I, (Pol I) an essential enzyme for transcription of ribosomal DNA (rDNA). Inhibition of rDNA transcription with CX-5461 blocks ribosomal biogenesis and causes cell cycle arrest, cell death or senescence depending on the cell type. Using multiple mouse strains, we observed that platelet numbers rapidly (1 week) increased 1.6 0.1 fold when treated with therapeutic doses of CX-5461.